Candidate: Dr. Salazar is currently Assistant Professor of Pediatrics, board certified in pediatric infectious diseases with an MPH in Epidemiology. The applicant's long term goal is to become an independent investigator with expertise in translational international infectious disease research with emphasis on HIV and syphilis pathogenesis. His short term goals are: (1) To strengthen previously learned skills in epidemiology, biostatistics and clinical trial design; (2) To increase his expertise in advanced immunologic research; (3)To learn state-of-the-art retroviral molecular and microbiologic techniques at the Walter Reed Army Research Institute and implement these techniques at UCHC; (4)To conduct the proposed HIV-syphilis pathogenesis research plan within the time limit of the grant and present the findings at international and national meetings; (5)To submit research findings for publication in reputable scientific journals; (6)To apply and obtain extramural funding. Environment: The applicant will work closely with his mentors and collaborators from CCMC, UCHC, CIDEIM, in Cali, Colombia and Walter Reed in Washington D.C. Dr J. Radolf, a renowned spirochetologist and Dr. P Krause, a well established physician-scientist, will serve as primary mentors. Dr. N. Michael, from WRAIR will provide mentorship in HIV pathogenesis. Dr. N Saravia (Director of CIDEIM) has agreed to serve as both mentor and collaborator in the Cali site. Dr. K Spooner, an infectious disease clinician at WRAMC will help recruit HIV+ patients co-infected with syphilis seen at WRAMC. CCMC will provide oversight and academic support through an Advisory Committee chaired by Dr. M Cloutier, a successful physician scientist, and comprised of members from the Division of Research. Research: Syphilis is caused by the spirochetal pathogen Treponema pallidum and it is well recognized as a risk factor for transmission of HIV. The immunologic underpinnings of this interaction have not been well studied. We now hypothesize that (i) infection with T. pallidum induces local and systemic inflammatory changes conducive to increased HIV infectiousness and susceptibility and (ii) untreated early syphilitic infection increases viral load in patients coinfected with syphilis and HIV. In Aim 1 we will examine the local and systemic inflammatory response to infection with T. pallidum of particular relevance to HIV transmission and dissemination. To do so we will (a) utilize the strength of muttiparameter flow cytometry to study the expression of dermal inflammatory cells within syphilitic lesions and peripheral blood of patients with secondary syphilis and (b) study the ex vivo effects of T. pallidum on surface expression of HIV co-receptors by T-cells and dendritic cells and how this effect influences HIV infectiousness. In Aim 2 we will study the effect of secondary syphilis on viral load (VL) in HIV co-infected individuals. In this aim we will compare VL between HIV patients with and without syphilis and determine the effect of penicillin on VL.